Over the past two decades, a number of calcium channel antagonists of the 1,4-dihydropyridine class have been identified that bind to calcium channels and inhibit calcium flux. Another group of compounds, the more recently identified calcium agonists are also 1,4-dihydropyridines that bind to the calcium channel but increase calcium flux. The expression of agonist or antagonist activities of the dihydropyridines appears to be dependent both on transmembrane potential of the target cell and drug concentration.
The compounds of the present invention are 1,4-dihydropyridines which exhibit the ability to modulate calcium flux across calcium channels. These compounds exhibit beneficial cardiovascular activities such as increasing cardiac contractibility, decreasing heart rate, decreasing vascular resistance, decreasing rate pressure product (as an index of oxygen consumption) or producing class III antiarrhythmic activity. This pharmacological profile makes these compounds useful in cardiovascular diseases such as congestive heart failure.